Institute of General Pharmacology and Toxicology, University Hospital Frankfurt, Goethe University Frankfurt am Main, 60590 Frankfurt am Main, Germany.
Department of Nephrology, University Hospital Frankfurt, Goethe University Frankfurt am Main, 60590 Frankfurt am Main, Germany.
Int J Mol Sci. 2022 Apr 2;23(7):3952. doi: 10.3390/ijms23073952.
S1P and its receptors have been reported to play important roles in the development of renal fibrosis. Although S1P has barely been investigated so far, there are indications that it can influence inflammatory and fibrotic processes. Here, we report the role of S1P in renal inflammation and fibrosis. Male S1P knockout mice and wild-type mice on a C57BL/6J background were fed with an adenine-rich diet for 7 days or 14 days to induce tubulointerstitial fibrosis. The kidneys of untreated mice served as respective controls. Kidney damage, fibrosis, and inflammation in kidney tissues were analyzed by real-time PCR, Western blot, and histological staining. Renal function was assessed by plasma creatinine ELISA. The S1P knockout mice had better renal function and showed less kidney damage, less proinflammatory cytokine release, and less fibrosis after 7 days and 14 days of an adenine-rich diet compared to wild-type mice. S1P knockout ameliorates tubular damage and tubulointerstitial fibrosis in a model of adenine-induced nephropathy in mice. Thus, targeting S1P might be a promising goal for the pharmacological treatment of kidney diseases.
S1P 及其受体已被报道在肾纤维化的发展中发挥重要作用。尽管迄今为止对 S1P 的研究甚少，但有迹象表明它可以影响炎症和纤维化过程。在这里，我们报告了 S1P 在肾炎症和纤维化中的作用。雄性 S1P 敲除小鼠和野生型 C57BL/6J 背景小鼠喂食富含腺嘌呤的饮食 7 天或 14 天，以诱导肾小管间质纤维化。未处理的小鼠的肾脏作为各自的对照。通过实时 PCR、Western blot 和组织学染色分析肾脏损伤、纤维化和炎症。通过血浆肌酐 ELISA 评估肾功能。与野生型小鼠相比，富含腺嘌呤饮食 7 天和 14 天后，S1P 敲除小鼠的肾功能更好，肾脏损伤、促炎细胞因子释放和纤维化更少。S1P 敲除可改善腺嘌呤诱导的小鼠肾病模型中的肾小管损伤和肾小管间质纤维化。因此，靶向 S1P 可能是治疗肾脏疾病的一种有前途的药物治疗目标。
